Complement C3-α and C3-ß Levels in Synovial Fluid But Not in Blood Correlate With the Severity of Osteoarthritis Research Society International Histopathological Grades in Primary Knee Osteoarthritis.

BACKGROUND: Primary osteoarthritis (OA) is the most common cause of knee arthritis worldwide. The knee synovial fluid complement C3-ß chain levels have been shown to correlate with clinical symptoms of knee OA. It is not known whether the complement C3 in the synovial fluid is derived from the circulation or is produced locally in the knee. METHODS: Fifty primary OA patients undergoing a total knee arthroplasty procedure were evaluated for biochemical analyses of C3-α and C3-ß chains in the synovial fluid and blood plasma. These levels were corelated with the severity of corresponding knee OA based on the Osteoarthritis Research Society International (OARSI) grade. RESULTS: Both synovial C3-α and C3-ß levels correlated significantly with the severity of OA. Neither plasma C3-α levels nor C3-ß levels significantly correlated with OARSI grading. Neither synovial C3-α levels nor C3-ß correlated significantly with plasma C3-α or C3-ß levels, respectively. Synovial C3-α chain and C3-ß chain levels were significantly higher in the grade >6 group. In plasma, neither C3-α chain levels nor C3-ß chain levels were significantly different between the groups. Neither synovial C3-α nor C3-ß levels significantly correlated with plasma erythrocyte sedimentation rate or C-reactive protein levels. CONCLUSION: In knee primary OA, C3 seems to be produced and released locally into the synovial fluid instead of being derived from blood in the circulation. Synovial C3 levels, but not blood plasma C3, correlate with the histopathological severity of primary OA in the knee. Synovial C3 may be an important factor in the pathogenesis of primary OA clinical symptoms and a potential target for therapeutic intervention.

Impact of neuraxial analgesia on outcomes following radical cystectomy: A systematic review.

Radical cystectomy (RC) is associated with significant morbidity. Neuraxial analgesia is recommended by enhanced recovery after surgery guidelines, but largely supported by evidence extrapolated from colorectal surgery outcomes. We synthesized current evidence regarding short- and long-term outcomes associated with neuraxial analgesia versus patient controlled non-neuraxial analgesia following RC. PubMed, Embase, and Cochrane databases were searched for relevant studies published up to May 2020. Studies reporting complications, length of stay (LOS), pain score, opioid usage within 72 hours, overall survival, cancer-specific survival, and recurrence rate were included. Of 550 identified studies, 9 met criteria for inclusion. Four studies demonstrated a higher percentage of 90-day complications in the neuraxial analgesia cohort. Out of 6 studies reporting information regarding LOS, 4 demonstrated no improvement in LOS in the neuraxial cohort. A reduction in 72 hours post-RC opioid usage was observed in 2 out of 3 studies with available data. Information regarding post-RC pain scores were variable up to 3 days post-RC. One out of 2 studies with available data reported a significant association between neuraxial analgesia and an earlier time to recurrence. No significant associations were seen with respect to overall survival or cancer-specific survival. A majority of low-to-moderate quality evidence demonstrates neuraxial analgesia is associated with a higher rate of complications, variable information regarding pain control, no improvements in LOS, and no significant association with long-term oncological outcomes. Further research regarding the incorporation of nonopiate-based analgesic modalities into RC ERAS protocols is warranted.

Knee synovial fluid complement C3-ß chain levels correlate with clinical symptoms of knee osteoarthritis.

AIM: Early research found innate immune factor complement C3 in the synovial fluid (SF) and activated in serum of osteoarthritis (OA) patients. Whether synovial C3 comes from circulation, or is produced locally, is still unknown. It is also unclear whether synovial and circulating C3 is responsible to OA symptoms. A native C3 molecule consists of two chains, C3-α and C3-ß. Small fragments breaking down from C3-α chain in serum and SF were reported to be related to OA severity. Little is known if C3-ß chain is involved in the pathogenesis. METHOD: In this study, we evaluated these important areas by biochemical analyses of C3-α and C3-ß chains in both the SF and plasma of OA patients. RESULTS: Our results showed that C3-α and C3-ß levels in SF did not correlate with those in plasma, suggesting that synovial C3 is independently and locally produced, rather than being "leaked" from circulation. Synovial C3-ß but not C3-α levels correlated with pain, other OA symptoms, function in daily living, and sports/recreational activities. Plasma C3-ß levels only marginally correlated with pain, and plasma C3-α levels did not correlate with any of these OA symptoms. CONCLUSION: We present first-hand evidence that the clinical symptoms of OA are mainly associated with C3 in the local SF rather than systemic circulation, suggesting local factors in the etiopathogenesis. Future local targeted therapies for pain management may be more effective and safer.

Discharge Readiness after Propofol with or without Dexmedetomidine for Colonoscopy: A Randomized Controlled Trial.

BACKGROUND: Enhanced recovery protocols employ various approaches to minimize detrimental side effects of anesthetizing agents. The authors tested the hypothesis that adding low-dose dexmedetomidine to propofol for anesthesia in ambulatory colonoscopies, compared with propofol alone, would lower the propofol requirement, improve the intra-procedure hemodynamic state, and not increase time-to-discharge. METHODS: In this noninferiority, double-blind, randomized controlled trial, patients having colonoscopies received total IV anesthesia either with propofol and placebo (n = 50), or propofol and a bolus dose of dexmedetomidine, 0.3 µg/kg (n = 51). Additional propofol was administered to maintain a Bispectral Index score of 60. Following the procedure, readiness for discharge was assessed regularly using the Modified Post Anesthetic Discharge Scoring System until discharge criteria were met. The primary outcome was the percentage of patients meeting discharge criteria within 30 min from procedure end-time. RESULTS: Twenty-six of 51 (51%) patients receiving propofol-dexmedetomidine were ready for discharge by 30 min from procedure end time, compared with 44 of 50 (88%) receiving propofol (P < 0.001). Propofol consumption was lower in subjects receiving propofol-dexmedetomidine (140 µg · kg(-1) · min(-1)) compared to those receiving propofol (180 µg · kg(-1) · min(-1)) with P = 0.011. The lowest mean arterial pressure decreased further from baseline in those receiving propofol-dexmedetomidine (-30%; mean decrease -30 ±10.5 mmHg) compared to propofol (-21%; mean decrease, -22 ± 14.2 mmHg) with P = 0.003. There was no difference in incidence of bradycardia, with sustained bradycardia occurring in 3 of 51 (6%) patients receiving propofol-dexmedetomidine compared to 1 of 50 (2%) patients receiving propofol (P = 0.62). No apnea episodes requiring positive-pressure ventilation occurred in either group. CONCLUSIONS: For anesthesia in ambulatory colonoscopy, combining low-dose dexmedetomidine with propofol delayed discharge readiness and provoked hypotension compared to propofol alone.

Periarticular injection and continuous femoral nerve block versus continuous femoral nerve block alone on postoperative opioid consumption and pain control following total knee arthroplasty: Randomized controlled trial.

Continuous femoral nerve block (CFNB) has been used to prevent the breakthrough pain after total knee arthroplasty (TKA). Multimodal drug injection (PMDI) has also been shown to decrease opioid consumption and pain. We investigated whether the use of PMDI further improves analgesic and rehabilitation outcomes when used in conjunction with CFNB. This is a prospective randomized controlled study of 44 patients undergoing primary TKA. The treatment group (n = 23) received a PMDI of combined ropivacaine, epinephrine, ketorolac and morphine, and the controlled group (n = 21) received saline at wound closure. Total opioid consumption, pain scores, knee range of motion (ROM) outcomes, length of stay, and patient satisfaction were measured and compared. The total consumption of morphine is similar between the two groups (52.6 ± 40.6 vs. 41.5 ± 32.9, p = 0.325). The mean morphine consumption of the treatment group was significantly lower than the control at 4 h after surgery (4.2 ± 5.5 vs. 11.3 ± 8.1, p = 0.002) but comparable on POD1, POD2, and POD3. The mean pain scores were significantly higher in the treatment group than the control group at POD2 (at rest: 47.3 ± 29.1 vs. 23.8 ± 20.6, p = 0.004; after PT: 57.7 ± 25.4 vs. 35.2 ± 26.8, p = 0.007) and POD3 (at rest: 30.9 ± 30.3 vs. 14.8 ± 20.9, p = 0.045; after PT: 50.2 ± 30.6 vs. 29.0 ± 32.1, p = 0.035), and not significantly different at 4 h after surgery or at POD1. Mean maximal knee flexion ROM in degrees during active and active assisted mobilization showed no significant difference between the control and the treatment groups on POD2 and POD3. The mean length of stay of the treatment group is significantly longer than the control group (5.1 ± 2.1 vs. 3.8 ± 1.6, p = 0.032). At discharge, no significant difference exists between the two groups for mean patient satisfaction. The addition of PMDI led to a decrease in opioid consumption in the immediate postoperative period but with no significant difference in the total consumption within the first three days postoperatively. This finding provides an opportunity for appropriate preoperative treatment and education for both patients and caregivers.

Sonographic evaluation of lumbar interlaminar space opening in a variety of patient body positions for optimal neuraxial anesthesia delivery.

OBJECTIVE: To find the position that provided the most comfort, as well as the widest L3-L4 interlaminar space opening. DESIGN: Pilot study. SETTING: Operating room. PATIENTS: Thirty-two healthy volunteers. INTERVENTIONS: L3-L4 interlaminar space was measured on volunteers assuming a baseline position (sitting upright) and 5 study positions: (1) sitting in fetal position, (2) sitting on a table tilted at 30°, (3) sitting while hugging an exercise ball, (4) sitting with midcalves on the table's edge, and (5) lying on one side in fetal position. Interlaminar spaces were measured to determine which position resulted in the largest interlaminar space compared with baseline. The comfort level of each position was rated by subjects using a visual analogue scale from 1 to 10. MAIN RESULTS: The means of the interlaminar openings in all study positions were significantly different from baseline, with the "sitting fetal" having the greatest difference, (1.32mm, P<.001), followed by "hugging a ball" (0.94mm, P<.001) and "lying fetal" (0.92mm, P<.001). Alternatively, when using "sitting fetal" (a more commonly used position) as a comparative baseline, "hugging a ball" and "lying fetal" showed smaller but not significantly different interlaminar openings (Δ=-0.38mm, P value = .221 and Δ=-0.40mm, P value = .164, respectively)."Sitting on a tilted table" and "sitting midcalf" showed significantly smaller interlaminar openings (Δ=-0.52mm, P value = .025 and Δ=-0.72mm, P value < .001, respectively) when compared with the alternative baseline of "sitting fetal." Mean visual analogue scale scores for comfort showed that "hugging a ball" (7.8/10), "lying fetal" (7.5/10), and "sitting fetal" (7.2/10) positions had the highest ratings. CONCLUSIONS: Ultrasonographic measurements carried out on 32 subjects showed that "sitting fetal," "lying fetal," and "hugging a ball" positions provided the widest L3-L4 interlaminar openings. These 3 positions were also found to be more comfortable.